The proposed studies will investigate further the deleterious effects of E. coli endotoxemia and hemorrhagic shock on mitochondrial electron transfer and energy-producing reactions. The cellular causative factors leading to mitochondrial impairment will be examined. We will concern ourselves with the concomitant subcellular alterations in mitochondria, respiration, lysosomes, and ion concentrations in an attempt to define the primary mechanism underlying the shock-induced cellular damage. In addition to assays of isolated mitochondria and lysosomes, in vivo studies of tissue PO2 and pH (microelectrodes), and the redox state of mitochondrial pyridine nucleotides and flavoproteins (differential fluorometry) will be performed, at various stages during experimental hemorrhagic shock, endotoxemia and pure hypoxia. Biochemical and biophysical functional studies of sub-cellular organelles will be correlated with morphology, utilizing the electron microscope.